Primary hepatocellular carcinoma (PHC) is much less common among women than men throughout the world. Although the prevalence of chronic infection with hepatitis B virus (HBV), the major etiologic factor, is usually somewhat higher among men, this difference could account for only a small fraction of the gender difference in risk of PHC. Our preliminary data from Haimen County, China, suggest that PHC incidence rates among non-carriers of HBV are 2.9 times higher among men. The major gender difference is within the population of chronic HBV carriers, where we observed a 4.0-fold greater risk of PHC among males than females. The epidemiologic and biologic basis for the reduced risk of PHC in women is unknown, but several mechanisms have been proposed. We will study retrospectively a cohort of approximately 75,354 men and women in Haimen County, China (an endemic area for PHC) who were characterized as carriers (approximately 9%) or noncarriers of HBV in 1986. The Specific Aims are as follows: 1) To determine age- and sex-specific incidence rates of PHC in chronic HBV carriers and noncarriers. A retrospective cohort study of 41,030 women (3179 carriers) and 34,324 men (3600 carriers), identified in 1986, will be conducted using the Haimen County Cancer Registry. 2) To test whether women HBV carriers are a greater risk of dying from diseases other than PHC compared to carrier men or noncarrier women. Data from the Cancer Registry and death certificate information available through the Haimen County Anti-Epidemic Station will be used to determine the age- and sex- specific mortality rates by cause among carriers and non-carriers in the cohort between 1986 and 1992. 3) To evaluate gender differences in the rate of loss of chronic HBV infection. A random sample of the surviving members of the 1986 cohort will be re-tested for hepatitis B surface antigen (HBsAg). 4) To determine whether there are gender and carrier-status differences for other known or suspected risk factors for PHC. Additional information will be elicited from random sample re-tested under Aim 3 by questionnaire. [Serum samples will be stored for future testing of biologic markers of other risk factors.] 5) To evaluate the effects of reproductive factors on PHC incidence among women. First, the relationship of parity to PHC risk will be tested by collecting birth data from family planning records supplemented by interviews with women in the cohort or their surviving relatives. Second, data on PHC mortality from 1972 to 1992 in the Cancer Registry will be analysed by birth cohort. Family size changed radically after introduction of the Chinese government's "one child policy" in the mid-1970's, and this may correlate with a change in PHC risk.